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Emerg. Microbes Infect., Apr 04 2024, | https://doi.org/10.1080/22221751.2024.2339949 Mammalian Adaptation Risk in HPAI H5N8: A Comprehensive Model Bridging Experimental Data with Mathematical Insights

Santosh Chokkakula^1,#, Sol Oh^1,#, Won-Suk Choi^1,#, Chang Il Kim¹, Ju Hwan Jeong¹, Beom Kyu Kim¹, Ji-Hyun Park¹, Seong Cheol Min¹, Eung-Gook Kim², Yun Hee Baek^1,*, Young Ki Choi^3,*, Min-Suk Song^1,*

¹Department of Microbiology, Chungbuk National University, College of Medicine and Medical Research Institute, Cheongju, Chungbuk, Republic of Korea.

²Department of Biochemistry, Chungbuk National University, College of Medicine and Med-ical Research Institute, Cheongju, Chungbuk, Republic of Korea.

³Center for Study of Emerging and Re-emerging Viruses, Korea Virus Research Institute, In-stitute for Basic Science (IBS), Daejeon, Republic of Korea.

^#Contributed equally.

^*Corresponding Authors: Yun Hee Baek, Young Ki Choi, Min-Suk Song

Abstract

Understanding the mammalian pathogenesis and interspecies transmission of HPAI H5N8 virus hinges on mapping its adaptive markers. We used deep sequencing to track these markers over five passages in murine lung tissue. Subsequently, we evaluated the growth, selection, and RNA load of eight recombinant viruses with mammalian adaptive markers. By leveraging an integrated non-linear regression model, we quantitatively determined the influence of these markers on growth, adaptation, and RNA expression in mammalian hosts. Furthermore, our findings revealed that the interplay of these markers can lead to synergistic, additive, or antagonistic effects when combined. The elucidation distance method then transformed these results into distinct values, facilitating the derivation of a risk score for each marker. In vivo tests affirmed the accuracy of scores. As more mutations were incorporated, the overall risk score of virus heightened, and the optimal interplay between markers became essential for risk augmentation. Our study provides a robust model to assess risk from adaptive markers of HPAI H5N8, guiding strategies against future influenza threats.

논문정보

형식Research article
게재일2024년 04월 (BRIC 등록일 2024-05-09)
연구진국내 연구진
분야 의약학 > 감염의학

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